Week 11 Studio

Part 1: Ownership and Sharing Challenge

Many useful genetic parts are currently protected by patents. For example, "uses of green fluorescent protein" is protected by United States Patent #5,491,084. At least 200 more recent patents protect additional uses of various fluorescent proteins. Patents are a legislated form of "intellectual property" by which inventors are granted a limited-time monopoly (~17 years) during which they can control access to the patented technology (e.g., by selling exclusive or non-exclusive licenses). In establishing the U.S. patent system, the founders of our country wanted to balance the sharing of inventions (e.g., via the publishing of patent applications) while also encouraging the investment and profit needed to drive innovation.

For today's challenge, many of your classmates will act as the inventors and patent holders of various genetic parts; each patent holder may license the use of their patents for profit (exclusively or non-exclusively), or give away the rights for free. Other classmates will act as investors who are seeking to license the complete set of genetic parts needed to encode the now familiar Eau d'E.coli system.

The first investor who is able to acquire licenses for all the genetic parts needed to encode the full Eau d'E.coli system will earn $100 in real cash money. This winning investor (if any) will be required to pay all inventors whatever fees might have been negotiated in obtaining the rights to use various genetic parts. If the promised fees are less than $100 then the investor can keep any additional cash. If the promised fees are greater than $100 then the investor must pay all additional licensing fees out of their own cash reserves.

The 12 components needed to produce a full Eau d'E.coli system are:

A genetically encoded "inverter"

A "constitutive PoPS source"

A "stationary phase PoPS source"

A "transcription terminator"

A "weak ribosome binding site"

A "strong ribosome binding site"

The gene encoding the "ATF1" enzyme

The gene encoding the "BSMT" enzyme

The gene encoding the "PCHA" enzyme

The gene encoding the "PCHB" enzyme

The gene encoding the "BAT2" enzyme

The gene encoding the "THI3" enzyme

Good luck and, perhaps, great profits!

After the challenge, consider the following questions:

Was it easy or difficult to license parts?

What determined the value of a part? Did inventors tend to overvalue parts? Did investors tend to undervalue parts?

Were any parts licensed for free? Why?

The challenge system in today's class contained 12 parts. Would it be easier or more difficult to license the parts for a system that contained fewer parts (e.g., 3 parts)? What about more parts (e.g., 100 parts)?

Part 2: Project Redesign Day 2

The rest of Wednesday's class is for working on projects. There's today, tomorrow and next week left to work!

Poem 4

I have dried
the shirt
made of 100% cotton
that was on your floor
and which
you were probably
planning
to air dry
Forgive me
if you had sorted
your own laundry
it would not be
so short
and so small

If you wanted to write your own spoof of the William Carlos Williams poem, you might begin by comparing the structure of these four poems. As a starting point they can be broken into 5 elements, namely

2 part situation

“forgive me,” and

2 part explanation.

For each poem, these elements are:

Situation (part 1)

Situation (part 2)

Forgive me

Explanation (part 1)

Explanation (part 2)

I have eaten the plums that were in the icebox

and which you were probably saving for breakfast

Forgive me

they were delicious

so sweet and so cold

Last evening we went dancing

and I broke your leg

Forgive me

I was clumsy

and I wanted you here in the wards where I am the doctor

I chopped down the house

that you had been saving to live in next summer.

I am sorry,

but it was morning, and I had nothing to do

and its wooden beams were so inviting.

I have dried the shirt made of 100% cotton that was on your floor

and which you were probably planning to air dry

Forgive me

if you had sorted your own laundry

it would not be so short and so small

Mix & Match Poetry

Now we can try to swap these poetic elements to see what interesting and clever spoofs we write. How about:

Situation (part 1)

Situation (part 2)

Forgive me

Explanation (part 1)

Explanation (part 2)

I have eaten the plums that were in the icebox

and I broke your leg

Forgive me

but it was morning, and I had nothing to do

and I wanted you here in the wards where I am the doctor

That seems to work but is it better? Let's try again:

Situation (part 1)

Situation (part 2)

Forgive me

Explanation (part 1)

Explanation (part 2)

I chopped down the house

and which you were probably planning to air dry

Forgive me

they were delicious

it would not be so short and so small

Well shoot, that's horrible. For one thing: It doesn't say anything understandable---this can be broadly described as a problem of functional compostion. For another thing: the connection between the different elements is, well, "awkward" at best---this can be broadly described as a problem of physical composition. If physical and functional composition of poems were working perfectly then every part would grammatically connect to the ones that flank it, and the meaning of the connected pieces would be interpretable at worst and clear at best.

Part 2: Genetic Parts

The physical and functional assembly of the poetic parts can be mapped to biological engineering once we define what a genetic "part" is. Let's start by extending what we did with the William Carlos Williams poem, namely let's consider a few natural genetic compositions, see what common elements compose them, and then try to bin these so we might compose new genetic elements by mixing and matching parts.

The bacterial lac operon is one we're already familiar with from our conversation with Jon Beckwith earlier in the term.

There are several genes encoded by this composition. LacI is made and we can see it's flanked by a promoter and a terminator. Lac Z, Y, and A are also made and they are flanked by a promoter + an operator on one end and a terminator on the other. So some genetic parts we might consider naming are:

promoter

operator

protein-coding gene

transcriptional terminator

Recombinant DNA technology gives us great power to move pieces of DNA around but it doesn't answer all the questions we might have about the resulting composition. For instance, are promoters/operators/genes and terminators all the parts we need to write a genetic program. Would the promoter that's in front of LacI make sense in front of LacZ, Y, and A? Is there something important about the junction of the parts?
An introduction to systematic examination and nomenclature of genetic parts, watch Device dude and Systems Sally's introduction to Parts

Part 3: The Registry of Standard Biological Parts

The animation ends with a screen shot from the BioBricks Foundation a not-for-profit organization that "encourages the development and responsible use of technologies based on BioBrick™ standard DNA parts that encode basic biological functions." BioBricks™ represent one kind of standard biological parts, standardized to enable reliable physical composition.

Just as we mixed and matched poetic elements, here are some mixed and matched genetic elements made from BioBrick™ parts.

Just as we could identify "forgive me"-ish elements in the "this is just to say poems" we can see common elements in these genetic compositions: the green arrow element which is = a promoter, but which comes in different flavors (I13452, R0040 or R0011), the red stop signs = transcriptional terminators (B0010, B0012).